Aza With or Without ATRA in Newly Diagnosed Unfit AML or Intermediate,High or Very High Risk MDS

NCT05175508 | Unknown Phase 2

• 1 other identifier: SOOCHOW-HY-2021-03
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, open-label, multicenter study to compare the efficacy and safety of AZA with or without ATRA in newly diagnosed unfit AML or Intermediate,High or Very High Risk MDS

Conditions

AML; MDS; Old Age; Debility; Hematologic Cancer

Keywords

acute myeloid leukemia; myelodysplastic syndromes; all-trans retinoic acid; azacitidine

Outcome Measures

Primary Outcomes (3)

• Overall Response Rate （ORR)

  Number of participants (responders) achieving ORR after the 6 cycle treatments，Overall response rate (ORR) based on the International Working Group (IWG)-2006 criteria, which include complete remission (CR), partial remission (PR), and major hematologic improvement (HI).

  6 months

• Overall survival (OS)

  time from randomization to death from any cause, or last known date to be alive.

  24months

• Progression-free survival (PFS)

  Progression-free survival (PFS) will be measured from time of enrolling in the clinical trial to the date on which disease progresses or the date on which the patient dies, whichever comes first.

  24 months

Secondary Outcomes (2)

• Percentage of Participants Achieving Transfusion Independence (TI) Who are Transfusion Dependent at Baseline

  6 months

• Incidence of systemic infections

  6 months

Study Arms (2)

Azacytidine Combined With ARTA

EXPERIMENTAL

Azacytidine 75mg/m2/d by IV on days 1-7 of every cycle with ATRA 20mg tid by po on days 1-21 of every cycle 28 days

Drug: Azacitidine; Drug: all trans retinoic acid

Azacytidine

EXPERIMENTAL

Azacytidine 75mg/m2/d by IV on days 1-7 of every cycle

Drug: Azacitidine

Interventions

Azacitidine DRUG

Azacytidine 75mg/m2/d by IV on days 1-7 of every cycle 28 days

Also known as: AZA

Azacytidine; Azacytidine Combined With ARTA

all trans retinoic acid DRUG

ATRA 20mg tid by po on days 1-21 of every cycle 28 days

Also known as: ATRA

Azacytidine Combined With ARTA

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Chinese guidelines for the diagnosis and treatment of acute myeloid leukemia (2017 edition)，excludes acute promyelocytic leukemia (M3、APL) and myelodysplastic syndromes(2017 edition)
• Be at least 18 years of age on day of signing informed consent
• Not suitable for newly diagnosed patients with intensive chemotherapy
• Not suitable for newly diagnosed patients with receiving hematopoietic stem cell transplantation
• The proportion of blast cells was below 50% in bone marrow
• Total white blood cell (WBC) count ≤10,000/µL；Must be able to swallow tablets

You may not qualify if:

• Malignant neoplasms with other progression
• Serious mental illness uncooperative
• Refusal to join the study

Sponsors & Collaborators

• The First Affiliated Hospital of Soochow University: lead

Study Sites (1)

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215006, China

RECRUITING

Related Publications (11)

• Chinese Society of Hematology, Chinese Medical Association. [Chinese guidelines for diagnosis and treatment of myelodysplastic syndromes (2019)]. Zhonghua Xue Ye Xue Za Zhi. 2019 Feb 14;40(2):89-97. doi: 10.3760/cma.j.issn.0253-2727.2019.02.001. No abstract available. Chinese.

  PMID: 30831622 BACKGROUND

• Leukemia & Lymphoma Group, Chinese Society of Hematology, Chinese Medical Association. [Chinese guidelines for diagnosis and treatment of adult acute myeloid leukemia (not APL) (2017)]. Zhonghua Xue Ye Xue Za Zhi. 2017 Mar 14;38(3):177-182. doi: 10.3760/cma.j.issn.0253-2727.2017.03.001. No abstract available. Chinese.

  PMID: 28395438 BACKGROUND

• Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Recher C, Sandhu I, Bernal del Castillo T, Al-Ali HK, Martinelli G, Falantes J, Noppeney R, Stone RM, Minden MD, McIntyre H, Songer S, Lucy LM, Beach CL, Dohner H. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015 Jul 16;126(3):291-9. doi: 10.1182/blood-2015-01-621664. Epub 2015 May 18.

  PMID: 25987659 BACKGROUND

• Delia M, Carluccio P, Buquicchio C, Vergine C, Greco G, Amurri B, Melpignano A, Melillo L, Cascavilla N, Guarini A, Capalbo S, Tarantini G, Mazza P, Pavone V, Di Renzo N, Specchia G. Azacitidine in the treatment of older patients affected by acute myeloid leukemia: A report by the Rete Ematologica Pugliese (REP). Leuk Res. 2015 Aug 20:S0145-2126(15)30358-1. doi: 10.1016/j.leukres.2015.08.005. Online ahead of print.

  PMID: 26364798 BACKGROUND

• Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A, Schoch R, Gattermann N, Sanz G, List A, Gore SD, Seymour JF, Bennett JM, Byrd J, Backstrom J, Zimmerman L, McKenzie D, Beach C, Silverman LR; International Vidaza High-Risk MDS Survival Study Group. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009 Mar;10(3):223-32. doi: 10.1016/S1470-2045(09)70003-8. Epub 2009 Feb 21.

  PMID: 19230772 BACKGROUND

• Pappa V, Anagnostopoulos A, Bouronikou E, Briasoulis E, Kotsianidis I, Pagoni M, Zikos P, Tsionos K, Viniou N, Meletis J, Papadaki H, Kioumi A, Galanopoulos A, Vervessou EC, Poulakidas E, Karmas P, Karvounis K, Symeonidis A. A retrospective study of azacitidine treatment in patients with intermediate-2 or high risk myelodysplastic syndromes in a real-world clinical setting in Greece. Int J Hematol. 2017 Feb;105(2):184-195. doi: 10.1007/s12185-016-2115-y. Epub 2016 Nov 4.

  PMID: 27815858 BACKGROUND

• Xiang L, Zhou J, Gu W, Wang R, Wei J, Qiu G, Cen J, Xie X, Chen Z. Changes in expression of WT1 during induced differentiation of the acute myeloid leukemia cell lines by treatment with 5-aza-2'-deoxycytidine and all-trans retinoic acid. Oncol Lett. 2016 Feb;11(2):1521-1526. doi: 10.3892/ol.2015.4052. Epub 2015 Dec 23.

  PMID: 26893773 BACKGROUND

• Xiang L, Wang R, Wei J, Qiu G, Cen J, Hu S, Xie X, Chen Z, Gu W. Retinoic acid receptor-beta gene reexpression and biological activity in SHI-1 cells after combined treatment with 5-aza-2'-deoxycytidine and all-trans retinoic acid. Acta Haematol. 2015;133(3):279-86. doi: 10.1159/000367586. Epub 2014 Nov 20.

  PMID: 25413479 BACKGROUND

• Xiang L, Dong W, Wang R, Wei J, Qiu G, Cen J, Chen Z, Zheng X, Hu S, Xie X, Cao X, Gu W. All-trans retinoic acid enhances the effect of 5-aza-2'-deoxycytidine on p16INK4a demethylation, and the two drugs synergistically activate retinoic acid receptor beta gene expression in the human erythroleukemia K562 cell line. Oncol Lett. 2014 Jul;8(1):117-122. doi: 10.3892/ol.2014.2133. Epub 2014 May 12.

  PMID: 24959230 BACKGROUND

• Wu W, Lin Y, Xiang L, Dong W, Hua X, Ling Y, Li H, Yan F, Xie X, Gu W. Low-dose decitabine plus all-trans retinoic acid in patients with myeloid neoplasms ineligible for intensive chemotherapy. Ann Hematol. 2016 Jun;95(7):1051-7. doi: 10.1007/s00277-016-2681-3. Epub 2016 Apr 26.

  PMID: 27116384 BACKGROUND

• Lubbert M, Grishina O, Schmoor C, Schlenk RF, Jost E, Crysandt M, Heuser M, Thol F, Salih HR, Schittenhelm MM, Germing U, Kuendgen A, Gotze KS, Lindemann HW, Muller-Tidow C, Heil G, Scholl S, Bug G, Schwaenen C, Giagounidis A, Neubauer A, Krauter J, Brugger W, De Wit M, Wasch R, Becker H, May AM, Duyster J, Dohner K, Ganser A, Hackanson B, Dohner H; DECIDER Study Team. Valproate and Retinoic Acid in Combination With Decitabine in Elderly Nonfit Patients With Acute Myeloid Leukemia: Results of a Multicenter, Randomized, 2 x 2, Phase II Trial. J Clin Oncol. 2020 Jan 20;38(3):257-270. doi: 10.1200/JCO.19.01053. Epub 2019 Dec 3.

  PMID: 31794324 BACKGROUND

MeSH Terms

Conditions

Frailty; Hematologic Neoplasms; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Azacitidine; Tretinoin

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Vitamin A; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Diterpenes; Pigments, Biological; Biological Factors

Study Officials

• Han Yue, Ph.D

  The First Affiliated Hospital of Soochow University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Han Yue, Ph.D

CONTACT

(0086)51267781856; hanyue@suda.edu.cn

Wu Depei, Ph.D

CONTACT

(0086)51267781856; drwudepei@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2021
• First Posted: January 3, 2022
• Study Start: May 1, 2021
• Primary Completion: May 1, 2022
• Study Completion: May 1, 2023
• Last Updated: January 3, 2022

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)